All references cited in this specification, and their references, are incorporated by reference herein in their entirety where appropriate for teachings of additional or alternative details, features, and/or technical background.
The invention relates in embodiments disclosed herein to a novel medical device with a coating. Such device may be configured for implantation into vessels or luminal structures within the body. More particularly, the present invention in embodiments relates to stents and synthetic grafts which are coated with a controlled-release matrix comprising a medicinal substance for direct delivery to the surrounding tissues, and a ligand attached thereto for capturing progenitor endothelial cells that may be found in the bodily fluids contacting the matrix (e.g., blood-contacting surface). The captured cells may result in the formation of mature endothelium at site of injury. In particular, a polymer matrix/drug/ligand-coated stent may be used, for example, in therapy of diseases such as restenosis, artherosclerosis, and endoluminal reconstructive therapies.
A medical device of embodiments of the present invention may comprise a polymer composition comprising a base material formed from, or including, a bioabsorbable polymer, copolymer, or terpolymer. The base material may further comprise a copolymer or terpolymer additive. One advantageous base material allows for a “soft” breakdown mechanism allowing for the breakdown of the component polymers to be less injurious to the surrounding tissue.
A persistent problem associated with the use of metallic devices such as stents in treating cardiovascular disease is the formation of scar tissue coating of the stent at the site of implantation the so-called process of restenosis. Moreover, metallic or polymeric non-absorbable stents may prevent vascular lumen remodeling and expansion. Numerous approaches have been tried to prevent scar tissue, and reduce complement activation of the immune response, which may be attendant to such implanted devices. Furthermore, an advantageous implant with a reduced inflammatory response and lower potential for trauma upon break-up of an implant and/or its component materials may be desired. A desirable improvement target may be found in the need for increased flexibility of shane and structure of medical devices for implantation, particularly into blood vessels.
Reference is made to U.S. Pat. No. 6,607,548 B2 (Inion), issued Aug. 19, 2003, which discloses compositions that are biocompatible and bioresorbable using a lactic acid or glycolic acid based polymer or copolymer blended with one or more copolymer additives. As a result, implants made from these blends are said to be cold-bendable without crazing or cracking. EP 0401844 discloses a blend of Poly-L-lactide with Poly D-DL-lactide.
It may be argued that bioabsorbable medical devices (such as stents) may be more suitable in the treatment of vascular disease than non-bioabsorbable medical devices. For example, it is known that non-biodegrable metallic stents can induce thrombosis by irritation of the blood vessel after since they are permanently embedded in the blood vessel. Further, their mechanical properties may deteriorate impairing blood vessel properties.
Coated medical devices are available commercially and approved by the FDA. For example, drug eluting stents containing anti-cancer drugs such as rapamycin and paclitaxel are commonly implanted into coronary arteries and have become the preferred method for used in percutaneous coronary interventions, because of their significant ability to reduce restenosis rates. One limitation of drug eluting stents has been that the patient needs to take supplemental oral drugs, such as aspirin and clopidrogel to prevent thrombosis from occurring at an early stage after implantation. Furthermore, the polymers used as a vehicle for drug delivery in some devices may induce vessel irritation, endothelial cell dysfunction, vessel hypersensitivity and chronic inflammation at the site of stent implantation (Waksman 2006).
The present inventors have recognized that it may be advantageous to develop a compatible polymer blends for medical devices, such as stents and vascular synthetic grafts, which provide a toughening mechanism to the base polymer when deployed into the body. In one embodiment, the base polymer composition may be used to impart additional molecular free volume to the base polymer to affect molecular motion sufficiently to allow for re-crystallization to occur at physiological conditions, for example, upon the addition of molecular strain in deployment. They have further recognized that increased molecular free volume can also increase the rate of water uptake adding both a plasticizing effect as well as increasing the bulk degradation kinetics. The composition may be formulated to allow for a “soft” breakdown mechanism such that the breakdown proceeds while being friendly to the surrounding tissue (less inflammatory response, and rendering lower potential for trauma upon break up of an implant). By selecting a polymer or copolymer for either the base or the additive or both, an enhanced hydrophilic property of the polymer blend may reduce complement activation and minimize or prevent opsonization. (see Dong and Feng, J of Biomedical Materials Research part A DOI 10.1002, 2006).